Abstract: TH-PO023

The RS6677604 in Complement Factor H Is Associated with Long Term Graft Function in Transplant Recipients with IGA Nephropathy

Session Information

Category: Transplantation

  • 1702 Transplantation: Clinical and Translational

Authors

  • Pesce, Francesco, University of Bari, Bari, Italy
  • Mininni, Donata, Policlinico di Bari, Bari, Italy
  • Margiotta, Marcella, Policlinico di Bari, Bari, Italy
  • Lucarelli, G., University of Bari, Bari, Italy
  • Battaglia, Michele, University of Bari, Bari, Italy
  • Gesualdo, Loreto, University of Bari, Bari, Italy
  • Castellano, Giuseppe, University of Bari, Bari, Italy
  • Stea, E. D., University of Bari, Bari, Italy
  • Crispino, Anna lucia, Policlinico di Bari, Bari, Italy
  • Accetturo, Matteo, University of Bari, Bari, Italy
  • Cianciotta, Francesca, University of Bari, Bari, Italy
  • Divella, Chiara, University of Bari, Bari, Italy
  • Rossini, M., University of Bari, Bari, Italy
  • Laghetti, Paola, University of Bari, Bari, Italy
  • Pontrelli, Paola, University of Bari, Bari, Italy
Background

BACKGROUND
The rs6677604 in Complement Factor H (CFH) and the deletion of complement factor H-related genes 1 and 3(CFHR3-1Δ), which is in linkage disequilibrium (LD) with rs6677604-A, have been associated with the development of IgA nephropathy (IgAN). IgAN has a negative outcome on renal transplantation. We tested the role of CFHR3-1Δ using rs6677604 as proxy, in IgAN patients who received a kidney transplant assessing the impact on long-term graft survival.

Methods

Our cohort consisted of 67 patients with a biopsy-proven diagnosis of IgAN on native kidneys that received a kidney transplant at the University of Bari (D.E.T.O.) between 1993 and 2017. Genomic DNA was extracted using standard techniques. The complement factor H (CFH) region containing the SNP rs6677604 was amplified through PCR and sequenced by Sanger technology. Relevant clinical parameters were retrieved from patients’ files and periodically recorded during the follow-up. Univariate and multivariate survival analyses were performed with eGFR < 60mL/min/1.73m2 as endpoint.

Results

Of 67 patients, 22 (32.8%) had the rs6677604-AG genotype and 45 (67.2%) the rs6677604-GG genotype. These two groups were comparable in terms of demographic characteristics, donor features and transplant-related factors such as the occurrence of delayed graft function, episodes of acute rejection and therapeutic regimen. No difference was found when we analyzed the progression of the disease before the transplant. However, we observed a significantly worse outcome of the graft in patients with the rs6677604-GG genotype by univariate survival analysis (P=5.81E-05) during the follow-up (69 ± 62 months). A multivariate Cox survival analysis revealed that the rs6677604-GG genotype (HR 30.8; 95% IC 3.3-285.5; P=0.003) is the strongest independent predictor for the graft outcome in a model adjusted for age, gender, delayed graft function, episodes of acute rejection, HLA match and donor specific antibodies.

Conclusion

Our study suggests a major impact of CFHR3-1Δ on long term graft function in kidney transplant recipients with IgAN and that rs6677604 typing can be used to predict the outcome in these patients.